ArticleProceedings of the National Academy of Sciences of the United States of America2022
LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Flavokawain A inhibits high glucose-induced malignant progression of lung cancer cells by suppressing PRMT5-mediated PTEN neddylation and nuclear translocation.Oncology letters · 2026Article
- Mendelian randomization and single-cell transcriptomics prioritize CD7 and LAPTM5 in primary Sjögren's disease: an integrative multi-omics analysis.Clinical rheumatology · 2026Article
- LAPTM5 Downregulation-Driven VAMP8 Phosphorylation Impairs Autophagosome-Lysosome Fusion and Aggravates Septic Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sex-specific trajectories of nonlinear immune aging at single-cell level.Nature communications · 2026Article
- LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- Laptm4a mediates renal ischemia-reperfusion injury by regulating the UNC5B-AKT/mTOR signaling pathway.Frontiers in immunology · 2026Article
- Enhanced WWP2 Exacerbates Podocyte Injury in Lupus Nephritis through Monoubiquitylating H2A at K119.International journal of biological sciences · 2026Article
- WWP2 in immune surveillance and antigen presentation: context-dependent roles in B cells, T cells, and tumor immune escape.Frontiers in immunology · 2026Review
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- LAPTM5 drives omental metastasis in high-grade serous ovarian cancer via TGF-β/Smad-mediated epithelial plasticity.Journal of translational medicine · 2025Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea.Communications biology · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Molecular profiles of the great obstetrical syndromes reveal common features and dynamic changes in early pregnancy.Communications medicine · 2025Article
- LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation.Nature communications · 2025Article
- WDFY4 Promotes the Progression of Atherosclerosis by Regulating Ferroptosis Mediated by the LAPTM5/CDC42/mTOR/4EBP1/SLC7A11 Pathway.Journal of cellular and molecular medicine · 2025Article
- Identification of crucial genes for polycystic ovary syndrome and atherosclerosis through comprehensive bioinformatics analysis and machine learning.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025Article
- LINC02888 promotes HGSOC progression and immune evasion via PPIB-mediated stabilization of LAPTM5 mRNA and inhibition of RIG-I-like receptor signaling.Journal of translational medicine · 2025Article
- Bioinformatics analysis of intrinsic drivers of immune dysregulation in multiple myeloma to elucidate immune phenotypes and discover prognostic gene signatures.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elimination of autoreactive developing B cells is an important mechanism to prevent autoantibody production. However, how B cell receptor (BCR) signaling triggers apoptosis of immature B cells remains poorly understood. We show that BCR stimulation up-regulates the expression of the lysosomal-associated transmembrane protein 5 (LAPTM5), which in turn triggers apoptosis of immature B cells through two pathways. LAPTM5 causes BCR internalization, resulting in decreased phosphorylation of SYK and ERK. In addition, LAPTM5 targets the E3 ubiquitin ligase WWP2 for lysosomal degradation, resulting in the accumulation of its substrate PTEN. Elevated PTEN levels suppress AKT phosphorylation, leading to increased FOXO1 expression and up-regulation of the cell cycle inhibitor p27Kip1 and the proapoptotic molecule BIM. In vivo, LAPTM5 is involved in the elimination of autoreactive B cells and its deficiency exacerbates autoantibody production. Our results reveal a previously unidentified mechanism that contributes to immature B cell apoptosis and B cell tolerance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.